The study is a five-year randomized double-blind clinical trial designed to evaluate the effectiveness of low-dosage levels of isotretinoin in reducing the incidence of basal cell corcinomas in a high-risk population, and to examine possible side effects associated with long-term administration of low doses of isotretinoin. Approximately 1,800 evaluable subjects will be entered into the study within 12-18 months at ten participating clinical centers located around the country (military and Veterans Administration hospitals). at each center, subjects will be stratified and randomly allocated to intervention (10 mg/day) or control (placebo) groups. Vitamin A and its analogs, collectively known as retinoids, have been actively studied for several years in relation to their requirements in normal physiology and health, as well as for their potential in prevention of human disease. This vitamin is necessary for the differentiation of epithelial cells and is essential for the development and function of growth, reproduction, and vision. Deprivation or deficiency of vitamin A promotes tissue metaplasia and neoplasia in various animal and organ culture models. Supplementation with retinoids can reverse these changes and restore functions of cell growth and differentiation in various cell lines. Laboratory experiments have shown that retinoids administered to animals can prevent chemical carcinogenesis. Since in most of the experiments animals were administered retinoids after their exposure to the carcinogen, the prophylactic effect of the retinoids is believed to be in the post-initiation phase, i.e., during promotion of carcinogenesis. In addition, several epidemiological studies have shown an association of low dietary intake or serum levels of vitamin A with increased risk of cancer, notably lung cancer, and other tumors of epithelial origin. Recent case reports have shown that isotretinoin can prevent the appearance of new basal cell carcinomas for four years in patients at high risk of developing new tumors.